Primary analysis of a multicenter, randomized clinical trial suggests that endocrine therapy demonstrates benefits over capecitabine when used as a maintenance therapy after first-line combination chemotherapy in hormone receptor–positive, HER2-negative advanced metastatic breast cancer.
Within the clinical setting, standard maintenance therapy for hormone receptor–positive, HER2-negative metastatic breast cancer has included endocrine therapy and chemotherapy. However, no prospective trials have assessed which is superior. Jian Huang, MD, PhD, Department of Oncology, Zhejiang Cancer Hospital, Hangzhou, China, and colleagues assessed this in the OVERSTEP clinical trial, to provide clinical practice insight based on robust evidence.
In this multicenter, randomized, open-label, prospective clinical trial conducted in China, 181 patients with metastatic hormone receptor–positive, HER2-negative breast cancer were enrolled. Patients were aged between 18 and 70 years, had an Eastern Cooperative Oncology Group performance status of 0-1, and had not previously received chemotherapy for advanced/metastatic breast cancer. For first-line salvage chemotherapy, patients received capecitabine plus another chemotherapy drug for at least 4 cycles. Patients with an evaluable complete response, partial response, or stable disease were randomized 1:1 to receive either capecitabine monotherapy or endocrine therapy as maintenance treatment.
Stratification by endocrine resistance and visceral metastasis was performed, and randomization was done centrally. The primary end point was progression-free survival (PFS). Analyses were based on all patients who received ≥1 doses of maintenance therapy.
Approximately three-quarters of patients (N = 136; 75.14%) who were responsive to first-line salvage chemotherapy were subsequently randomized to receive either capecitabine or endocrine therapy as maintenance therapy.
After a median follow-up of 24.3 months (interquartile range, 20.46-37.25) in the endocrine maintenance therapy group and 24.1 months (interquartile range, 20.67-36.77) in the capecitabine maintenance therapy group, the hazard ratio (HR) for PFS was 0.625 (95% confidence interval [CI], 0.429-0.909; P = .013). Median PFS was 17.5 months (95% CI, 11.544-23.856) in the endocrine maintenance therapy group and 12.2 months (95% CI, 11.170-13.230) in the capecitabine maintenance therapy group.
In the endocrine-sensitive groups, median PFS was 29.3 months (95% CI, 14.605-43.995) in the endocrine maintenance therapy group and 14.8 months (95% CI, 7.445-22.155) in the capecitabine maintenance therapy group. The HR for PFS was 0.515 (95% CI, 0.269-0.988; P = .042). In the endocrine resistance group, the HR for PFS was 0.791 (95% CI, 0.499-1.253; P = .314) and the median PFS was 13.6 months (95% CI, 9.111-18.089) in the endocrine maintenance therapy group and 12.0 months (95% CI, 10.357-13.643) in the capecitabine maintenance therapy group.
In visceral metastasis group, the HR for PFS was 0.668 (95% CI, 0.410-1.089; P = .101). The median PFS was 14.3 months (95% CI, 11.113-17.487) in the endocrine maintenance therapy group and 11.0 months (95% CI, 8.140-13.860) in the capecitabine maintenance therapy group. In the nonvisceral metastasis group, the HR for PFS was 0.54 (95% CI, 0.300-0.972; P = .037), and median PFS was 25.3 months (95% CI, 15.278-35.322) in the endocrine maintenance therapy group and 17.0 months (95% CI, 10.783-23.217) in the capecitabine maintenance therapy group.
The investigators concluded that after first-line salvage combined chemotherapy for patients with hormone receptor–positive, HER2-negative metastatic breast cancer, endocrine therapy as maintenance therapy conferred a better survival benefit than chemotherapy, particularly for endocrine therapy–sensitive cases that were not visceral. They suggested that based on these data, endocrine therapy should be considered the preferred treatment for advanced/metastatic breast cancer after first-line combination chemotherapy.
Source: Huang J, Shao X, Cai L, et al. Primary analysis of OVERSTEP: A multicenter, randomized clinical trial of capecitabine or endocrine therapy as a maintenance therapy after the 1stline chemotherapy in hormone receptor positive and HER2-negative advanced/metastatic breast cancer. Presented at: 2020 San Antonio Breast Cancer Symposium, December 8-11, 2020. Abstract PS13-01.